1. Field of the Invention
This invention relates to a pharmaceutical composition for inhibiting osteoclast growth and, more particularly, to a plurality of the pharmaceutical composition comprising benzamide derivatives.
2. Description of the Related Art
The human bone is a highly dynamic organ that maintains its homeostasis through a delicate balance between bone formation and resorption, mediated by the bone-forming osteoblasts and the bone eroding osteoclasts. This balance between these two cells types results in bone remodeling, and this continues unless critical changes in the balance occur. Increased osteoclast activity induces thinning and trabecular bone erosion, resulting in many diseases of Bone, such as osteoporosis, periodontitis and osteoarthritis.
The osteoblasts arose from mesenchymal cells are responsible for the formation of bond. The specific transcription factor of osteoblasts, such as Runx2/cbfa1 (runt-related transcription factor-2) and osterix, can regulate the mesenchymal cells to precursor cell and introduce the formation of type I collagen, alkaline phophatase (ALP) and bone sailoprotein. The osteocalcin (OCN) and osteopontin formed in the later period which can promote the precursor cell to differentiate and process mineralization can create the star-shaped osteocytes forming the bone in bone base. In addition, the precursor cell can also divide to lining cells in flat shape and less organelle which are covered on the surface of the bond and introduce to modify the bone remodeling.
The osteoclasts arose from hematopoietic precursor cells. Furthermore, the Macrophage-Colony Stimulating Factor (M-CSF) and the Receptor Activator of Nuclear factor Kappa B Lignad (RANKL) secreted by the osteoblasts will combine with c-Fms and RANK on the cell membrane of the precursor cell, respectively, for increasing the secretions of tartrate-resistant acid phosphatase (TRAP), perform and appearance integrin b3 . . . etc. The changes of the activities of the proteins and the shape of the cell will improve the movement of the osteoclasts and the attaching ability of the osteoclasts on the bond surface. On the other hand, the presence of the enzyme, such as cathepsin K matrix metalloproteinase-9(MMP-9), dendritic cell-specific transmembrane protein (DC-STAMP), ATPase H+ transporting lysosomal V0 subunit D2 (ATP6V0D2), involved in the cell combination and the bone eroding will be presented, so as to introduce the precursor cell differentiating to the big and fully grown (radius of 20 to 100 mm) multi-nuclei cell including 4 to 20 cell nucleuses and the multi-nuclei cell will result in the bone eroding. The osteoblasts not only can secrete M-CSF and RANKL to promote the growing and differentiating of the osteoclasts, but also secrete osteoprotegerin (OPG). OPG will block the formation of the osteoclasts by combining with RANKL to prevent that RANKL combine with RANK. Restraining the formation of the osteoclasts will decrease the happening of the bone eroding. Moreover, OPG also involve the apoptosis of the osteoclasts.